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Title: Crystal Structure of the Mammalian GIRK2 K[superscript +] Channel and Gating Regulation by G Proteins, PIP[subscript 2], and Sodium

Abstract

G protein-gated K{sup +} channels (Kir3.1-Kir3.4) control electrical excitability in many different cells. Among their functions relevant to human physiology and disease, they regulate the heart rate and govern a wide range of neuronal activities. Here, we present the first crystal structures of a G protein-gated K{sup +} channel. By comparing the wild-type structure to that of a constitutively active mutant, we identify a global conformational change through which G proteins could open a G loop gate in the cytoplasmic domain. The structures of both channels in the absence and presence of PIP{sub 2} suggest that G proteins open only the G loop gate in the absence of PIP{sub 2}, but in the presence of PIP{sub 2} the G loop gate and a second inner helix gate become coupled, so that both gates open. We also identify a strategically located Na{sup +} ion-binding site, which would allow intracellular Na{sup +} to modulate GIRK channel activity. These data provide a structural basis for understanding multiligand regulation of GIRK channel gating.

Authors:
;  [1]
  1. Rockefeller
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
UNIVERSITY
OSTI Identifier:
1027666
Resource Type:
Journal Article
Journal Name:
Cell
Additional Journal Information:
Journal Volume: 147; Journal Issue: 1; Journal ID: ISSN 0092-8674
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; CONFORMATIONAL CHANGES; CRYSTAL STRUCTURE; GTP-ASES; PHYSIOLOGY; REGULATIONS; SODIUM

Citation Formats

Whorton, Matthew R, and MacKinnon, Roderick. Crystal Structure of the Mammalian GIRK2 K[superscript +] Channel and Gating Regulation by G Proteins, PIP[subscript 2], and Sodium. United States: N. p., 2011. Web. doi:10.1016/j.cell.2011.07.046.
Whorton, Matthew R, & MacKinnon, Roderick. Crystal Structure of the Mammalian GIRK2 K[superscript +] Channel and Gating Regulation by G Proteins, PIP[subscript 2], and Sodium. United States. doi:10.1016/j.cell.2011.07.046.
Whorton, Matthew R, and MacKinnon, Roderick. Thu . "Crystal Structure of the Mammalian GIRK2 K[superscript +] Channel and Gating Regulation by G Proteins, PIP[subscript 2], and Sodium". United States. doi:10.1016/j.cell.2011.07.046.
@article{osti_1027666,
title = {Crystal Structure of the Mammalian GIRK2 K[superscript +] Channel and Gating Regulation by G Proteins, PIP[subscript 2], and Sodium},
author = {Whorton, Matthew R and MacKinnon, Roderick},
abstractNote = {G protein-gated K{sup +} channels (Kir3.1-Kir3.4) control electrical excitability in many different cells. Among their functions relevant to human physiology and disease, they regulate the heart rate and govern a wide range of neuronal activities. Here, we present the first crystal structures of a G protein-gated K{sup +} channel. By comparing the wild-type structure to that of a constitutively active mutant, we identify a global conformational change through which G proteins could open a G loop gate in the cytoplasmic domain. The structures of both channels in the absence and presence of PIP{sub 2} suggest that G proteins open only the G loop gate in the absence of PIP{sub 2}, but in the presence of PIP{sub 2} the G loop gate and a second inner helix gate become coupled, so that both gates open. We also identify a strategically located Na{sup +} ion-binding site, which would allow intracellular Na{sup +} to modulate GIRK channel activity. These data provide a structural basis for understanding multiligand regulation of GIRK channel gating.},
doi = {10.1016/j.cell.2011.07.046},
journal = {Cell},
issn = {0092-8674},
number = 1,
volume = 147,
place = {United States},
year = {2011},
month = {11}
}